HEAT ACTIVATED MICROPARTICLE DRUG DELIVERY SYSTEMS

该项目的总体目标是开发热激活 用于递送药物的微粒药物递送系统 化疗药物可以与 热疗或热疗加放射治疗。 在第1阶段期间，微粒将由核黄素制备， 高级脂肪酸的甘油三酯酯，其在 温度为40-45 ℃。 选择核黄素作为模型 因为它比抗肿瘤药物的成本低得多， 剂. 将通过溶剂制备微球（1-10 am） 蒸发过程，其产生单块药物聚合物 矩阵 BIOTEK开发的一种新的微流化床工艺将 用于生产真正的壁/储库微胶囊， 药物完全被甘油三酯酯壁包围 材料 初步研究表明，微粒可以 有效地涂覆有甘油三酯。 微粒 将在体外评价药物的增量释放 温度从37摄氏度到45摄氏度。 此外他们 将被表征为药物含量、尺寸分布和 表面形态 最有希望的配方是 在小鼠体内评价。 I期研究将为进一步研究提供基础。 第11阶段工艺的开发和微胶囊化 化疗药物，这将受益于激活， 热疗 最终目标是完成 开发，进行必要的临床前试验，准备 IND文件，并开始临床研究， 完成SBIR第11阶段。

The overall objective of the project is to develop heat activated microparticle drug delivery systems for delivery of chemotherapeutic agents that could be used in conjunction with therapeutic hyperthermia or hyperthermia plus radiation. During Phase 1 microparticles will be prepared from Riboflavin and triglyceride esters of higher fatty acids which melt at a temperature of 40-45"C. Riboflavin was selected as a model compound because it is significantly less costly than antitumor agents. Microspheres (1-10 am) will be prepared by a solvent evaporation process which produces a monolithic drug polymer matrix. A new microfluidized bed process developed by BIOTEK will be used to produce true wall/reservoir microcapsules in which the drug is completely surrounded by a triglyceride ester wall material. Preliminary studies indicate that microparticles can be effectively coated with triglyceride esters. The microparticles will be evaluated in vitro release of the drug at incremental temperatures from 37degrees C to 45degrees C. In addition, they will be characterized as to drug content, size distribution, and surface morphology. The most promising formulation will be evaluated in vivo in mice. The Phase 1 studies will be provide the basis for further development of the process in Phase 11 and the microencapsulation of chemotherapeutic agents which would benefit from activation by therapeutic hyperthermia. The ultimate goal is to complete development, conduct necessary preclinical tests, prepare documentation for an IND, and to begin clinical studies by the completion of SBIR Phase 11.